title: Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study.
abstract: OBJECTIVE
  To address the need for nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens, we explored the virologic and pharmacokinetic characteristics of maraviroc plus ritonavir-boosted darunavir in a single-arm, open-label, 96-week study.
  
  
  METHODS
  Twenty-four antiretroviral-naive R5 HIV-1-infected participants received maraviroc 150 mg and darunavir/ritonavir (DRV/r) 800/100 mg (MVC/DRV/r) once daily. The primary outcome was virologic failure (VF) = confirmed viral load (VL) >50 copies per milliliter at week 24 in the modified intent-to-treat population. To determine viral dynamics, participant-specific first- and second-phase empirical Bayes estimates were compared with decay rates from efavirenz (EFV) plus lopinavir/ritonavir, lopinavir/ritonavir plus 2NRTIs, and EFV plus 2NRTIs. Maraviroc plasma concentrations were determined at weeks 2, 4, 12, 24, and 48.
  
  
  RESULTS
  Baseline median (Q1, Q3) CD4 count and VL were 455 (299, 607) cells per cubic millimeter and 4.62 (4.18, 4.80) log10 copies per milliliter, respectively. VF occurred in 3 of 24 participants {12.5% [95% confidence interval (CI): 2.7 to 32.4]} at week 24. One of these resuppressed, yielding a week 48 VF rate of 2/24 [8.3% (95% CI: 1.0 to 27.0)]. The week 48 failures were 2 of the 4 participants (50%) with baseline VL >100,000 copies per milliliter. Week 96 VF rate was 2/20 [10% (95% CI: 1.2 to 31.7)]. Phase 1 decay was faster with MVC/DRV/r than reported for ritonavir-boosted lopinavir plus 2NRTIs (P = 0.0063) and similar to EFV-based regimens. Individual maraviroc trough concentrations collected between 20 and 28 hours post dose (n = 59) was 13.7 to 130 ng/mL (Q1, 23.4 ng/mL; Q3, 46.5 ng/mL), and modeled steady-state concentration was 128 ng/mL.
  
  
  CONCLUSIONS
  MVC/DRV/r 150/800/100 mg once daily has potential for treatment-naive patients with R5 HIV-1.
authors.affiliation: *Division of Infectious Diseases, Northwestern University, Chicago, IL; †Division of Clinical Pharmacology, University of Alabama, Birmingham, AL; ‡University of Maryland, Baltimore, MD; §Statistical and Data Analysis Section, Harvard School of Public Health, Boston, MA; ‖Quest Clinical Research, San Francisco, CA; ¶Division of Infectious Diseases, University of Miami, Miami, FL; #CORE Center, Chicago, IL; **Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; ††Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC; and ‡‡Division of Infectious Diseases, University of Nebraska, Omaha, NE.
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Patrick
authors.initials: P
authors.lastname: Ryscavage
authors.forename: Baiba
authors.initials: B
authors.lastname: Berzins
authors.forename: Darlene
authors.initials: D
authors.lastname: Lu
authors.forename: Jay
authors.initials: J
authors.lastname: Lalezari
authors.forename: Jose
authors.initials: J
authors.lastname: Castro
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Adeyemi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Athe
authors.initials: A
authors.lastname: Tsibris
authors.forename: Susan
authors.initials: S
authors.lastname: Swindells
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069454:Darunavir; D004359:Drug Therapy, Combination; D005260:Female; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D000077592:Maraviroc; D010865:Pilot Projects; D020871:RNA Stability / Q000187:drug effects*; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D014230:Triazoles; D000077592:Maraviroc; D019438:Ritonavir; D000069454:Darunavir